Lymphadenopathy After COVID-19 Vaccine Mimicking Lymph-Node Progression in a Patient With Metastatic Melanoma Julia Verdaguer-Faja1, José Luis Manzano2, Sofía España2, Paula Cecilia Notta3, Raul Vicente Rodriguez Iniesta4, Aram Boada1,5 1 Dermatology Department. Hospital Universitari Germans Trias i Pujol. Universitat Autònoma de Barcelona. Badalona, Barcelona, España. 2 Medical Oncology Department. Hospital Universitari Germans Trias i Pujol. Universitat Autònoma de Barcelona. Badalona, Barcelona, España. 3 Nuclear Medicine-PET Department. Hospital Universitari de Bellvitge. Universitat de Barcelona. Hospitalet de Llobregat, Barcelona, España. 4 Radiology Department. Hospital Universitari Germans Trias i Pujol. Universitat Autònoma de Barcelona. Badalona, Barcelona, España. 5 Institut Investigació Germans Trias i Pujol (IGTP). Badalona, Barcelona, España. Citation: Verdaguer Faja J, Manzano JL, España S, Notta PC, Rodriguez Iniesta RV, Boada A. Lymphadenopathy After COVID-19 Vaccine Mimicking Lymph Node Progression in a Patient With Metastatic Melanoma. Dermatol Pract Concept. 2022;12(4):e2022171. DOI: https://doi.org/10.5826/dpc.1204a171 Accepted: February 19, 2022; Published: October 2022 Copyright: ©2022 Verdaguer Faja et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding author: Julia Verdaguer Faja, MD, Dermatology Department. Hospital Universitari Germans Trias I Pujol. Carretera de Canyet s/n. 08916. Badalona (Barcelona), Spain. Phone: 0034934978813, E-mail: verdaguer.ju@gmail.com Introduction Case presentation COVID-19 vaccination has been rapidly implemented A 47-year-old male with BRAF mutant melanoma of the worldwide, especially among patients with cancer. Local back and right axillar adenopathies underwent wide ex- reactions with ipsilateral lymphadenopathy are among the cision and lymphadenectomy and started adjuvant treat- most common side effects. A few cases of false-­positive ment with nivolumab. One month later, he presented 18 18-fluorodeoxyglucose ( FDG) PET/computed tomog- disease relapse with satellitosis and a contralateral ade- raphy (CT) scan after COVID-19 vaccination have been nopathy in the left axilla, the latter detected by PET-CT. reported [1,2]. This is especially important in oncologic Treatment was changed to targeted therapy (dabrafenib patients, such as in cutaneous melanoma, where these and trametinib), reaching complete remission. An FDG- findings might pose difficulties during their follow-up and PET/CT from February 2021 showed no active disease. management. In May 2021, after eight months of targeted therapy, a Letter to the Editor | Dermatol Pract Concept. 2022;12(4):e2022171 1 routine FDG-PET/CT showed substantial 18F-FDG avidity disease. Further questioning of the patient revealed that in the left axilla, with multiple malignant-appearing lymph he had received the second dose of the COVID-19 mRNA nodes; no other foci were identified (Figure 1A). Given vaccine (Moderna) in the left deltoid muscle 5 days prior this finding, up to two ultrasound-guided biopsies were to the routine PET/CT scan. Finally, a new PET/CT was performed on the left axilla, describing at least one clearly performed 4 months later and revealed complete resolu- malignant-appearing adenopathy in the ultrasound exam- tion of the hypermetabolic left axillary nodes (Figure 2), ination (Figure 1, B and C), and showing histologically suggesting the diagnosis of reactive lymphadenopathy due lymphoid hyperplasia with no evidence of microscopic to COVID-19 vaccine. Figure 1. Imaging tests performed in May 2021. (A-D) Routine ¹⁸F-FDG-PET/TC: hypermetabolic lymphadenopathy in the left axillary re- gion, the largest and with most metabolism of 13 mm (SUVmax: 3.9), suggestive of malignancy. (E) Sonographic exam of the left axilla after PET/CT findings: left axillary lymphadenopathy of rounded morphology with displacement of the central fatty hilum at the expense of great hypoechoic cortical thickening, sonographically suspicious. Core needle biopsy was taken from it. Figure 2. (A-D) 4-month control 18F-FDG-PET/TC, September 2021: normalization of hypermetabolic lymphadenopathies in the left axillary region: resolution of the pathologic nodal uptake. 2 Letter to the Editor | Dermatol Pract Concept. 2022;12(4):e2022171 Discussion appearance of hypermetabolic regional lymph nodes after its injection. Keeping this etiology in mind and following Transient FDG uptake in normal or enlarged lymph nodes some recommendations for scheduling the PET-CT is espe- (mainly axillary, supraclavicular and cervical nodes) has cially important when evaluating oncologic patients to avoid ­already been described after administration of several types of misinterpretation. vaccines [3,4]. This issue has also been observed now with the COVID-19 vaccination [1,2], being more frequently seen in pa- References tients vaccinated with Moderna, compared to Pfizer-BioNTech (72% versus 43%), and more intensely after the booster 1. Cohen D, Krauthammer SH, Wolf I, Even-Sapir E. Hypermetabolic lymphadenopathy following administration ­ ­administration. Furthermore, it has been most frequently seen of BNT162b2 mRNA Covid-19 vaccine: incidence assessed on day 1–7 after vaccination (71% of patients) and showed a by [18F]FDG PET-CT and relevance to study interpretation. negative correlation with time after vaccination [2]. Eur J Nucl Med Mol Imaging. 2021;48(6):1854-1863. DOI: This FDG avid axillary lymphadenopathy may confound 10.1007/s00259-021-05314-2. PMID: 33774684. PMCID: interpretation in oncologic patients and change patient man- PMC8003894. agement (eg excessive follow-up imaging studies, unneces- 2. Skawran S, Gennari AG, Dittli M, et al. [18F]FDG uptake of axil- lary lymph nodes after COVID-19 vaccination in oncological PET/ sary biopsies, treatment delays), besides causing additional CT: frequency, intensity, and potential clinical impact. Eur ­Radiol. patient anxiety [2]. This is the case of cutaneous melanoma, 2022;32(1):508-516. DOI: 10.1007/s00330-021-08122-2. where misinterpretation in tumor staging or disease response PMID: 34156552. PMCID: PMC8217971. during treatment may lead to deeply important differences in 3. Thomassen A, Lerberg Nielsen A, Gerke O, Johansen A, Petersen terms of disease prognosis and treatment algorithm. H. Duration of 18F-FDG avidity in lymph nodes after pandemic In order to avoid misinterpretation, it is therefore im- H1N1v and seasonal influenza vaccination. Eur J Nucl Med Mol Imaging. 2011;38(5):894-898. DOI: 10.1007/s00259-011 portant in oncologic patients to perform vaccination contra- -1729-9. PMID: 21340453. lateral to the tumor expected nodal drainage, to ask patients 4. McIntosh LJ, Bankier AA, Vijayaraghavan GR, Licho R, Rosen about recent vaccination, and to perform FDG PET/CT be- MP. COVID-19 vaccination-related uptake on FDG PET/CT: An fore or at least 2 weeks after (optimally 4–6 weeks after) emerging dilemma and suggestions for management. Am J Roent- vaccine administration, if possible [2,4,5]. genol. 2021;217(4):975-983. DOI: 10.2214/AJR.21.25728. PMID: 33646823. 5. McIntosh LJ, Rosen MP, Mittal K, et al. Coordination and opti- Conclusions mization of FDG PET/CT and COVID-19 vaccination; Lessons learned in the early stages of mass vaccination. Cancer Treat Rev. As COVID-19 vaccination has been rapidly implemented 2021;98:102220. DOI: 10.1016/j.ctrv.2021.102220. PMID: worldwide, clinicians should be aware of the transient 34029956. PMCID: PMC8110324. Letter to the Editor | Dermatol Pract Concept. 2022;12(4):e2022171 3